Search PubMed⌕ Search

Biomedical subjects

P J Wauben-Penris

Publications and source records attributed to P J Wauben-Penris.

16 recordsLinked to original sources
PubMed1998

Immunomodulatory effects of tretinoin in combination with clindamycin.

BACKGROUND: Since acne is a multifactorial skin disease, therapies affecting several etiologic factors can have a higher than expected effectiveness. A combination of the antibiotic clindamycin phosphate and the retinoic acid tretinoin was developed. OBJECTIVE: Anti-inflammatory and immunomodulatory effects of tretinoin in vitro were studied on human keratinocytes and peripheral blood mononuclear cells (PBMCs). Effects of clindamycin phosphate on tretinoin effects were studied. METHODS: Anti-inflammatory effects on keratinocytes were assessed using an in vitro model with PMA (phorbol ester)-stimulated A431 cells (human epidermoid carcinoma). Immunomodulatory effects were measured on superantigen (SEB) stimulated PBMCs. RESULTS: Tretinoin showed very potent inhibition of PMA-stimulated IL-6 (interleukin 6) release by A431 cells. The addition of clindamycin phosphate did not interfere with this effect. Tretinoin very potently stimulated IL-5 release, and inhibited IFN gamma release by SEB-stimulated human PBMCs. This indicates an immunomodulatory effect, stimulating Th2, and inhibiting Th1 dominated responses. These features have been related to the healing of acne lesions. The addition of clindamycin phosphate did not interfere with the immunomodulatory effects of tretinoin. CONCLUSION: The combination of tretinoin and clindamycin phosphate can be expected to be very effective in acne therapy.

Acne Vulgaris↗
PubMed1995

Corticosteroids class-dependently inhibit in vitro Th1- and Th2-type cytokine production.

Corticosteroids (CS) are very potent immunosuppressive agents and are widely used to treat inflammatory diseases. On the basis of their clinical efficacy and potency CS have been divided into different classes. In the present study we investigated whether the class-associated effects of CS are correlated with a differential in vitro effect on cytokine production by T lymphocytes. Therefore, we determined the in vitro effects of CS on the production of Th1- and Th2-type cytokines. The addition of CS, in the range of 10(-9) to 10(-4) M, resulted in a class- and dose-dependent inhibition of the production of both IFN-gamma and IL-4. Notably, at the lowest doses tested, hydrocortisone and hydrocortisone 17-butyrate had a stimulatory effect on IL-4 production. CS class-dependently inhibited the IL-2 production by T cells but did not affect IL-2R expression of the T cells. Addition of rIL-2 could not completely restore the inhibitory effect of the CS on proliferation and on IFN-gamma and IL-4 production, indicating that CS act only partially via inhibition of IL-2 production. The demonstrated positive correlation between the clinical efficacy and the in vitro effects of the different classes of CS strongly suggests that the effect of CS on T-cell-mediated inflammation follows from inhibition of proliferation and cytokine production by T lymphocytes. The in vitro method used will be valuable for investigating and classifying new types of CS and other substances for applications in T-cell-mediated diseases.

Adrenal Cortex Hormones↗
PubMed1995

Effects of topical treatment with budesonide on parameters for epidermal proliferation, keratinization and inflammation in psoriasis.

Corticosteroids are important in the treatment of inflammatory dermatoses, such as psoriasis. They have anti-inflammatory, anti-proliferative and immunosuppressive effects. In this study, the effect of budesonide on proliferation, inflammatory cells and cytokines in psoriasis was investigated. In order to elucidate the time course of the different effects of corticosteroid treatment in psoriasis, six patients were treated for 3 weeks with budesonide 0.025% ointment (Preferid), and biopsies were studied immunohistochemically, before treatment and after 1 and 3 weeks of treatment. Clinical scores together with staining with antibodies indicating proliferation, keratin 16, keratin 10, T-lymphocytes, monocytes, polymorphonuclear leukocytes, Langerhans cells, interleukin-1alpha (IL-1alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) were performed. 'Psoriasis area' and 'severity index' (PASI) scores were significantly reduced after 1 week and 3 weeks of treatment. Epidermal hyperproliferation (Ki-67 binding) and suprabasal keratin 16 (Ks8.12) expression decreased within 1 week, while keratin 10 (RKSE60) expression did not change. Five out of 6 patients showed cytokine levels (IL-1alpha, IL-6, IL-8, and TNF-alpha; detected immunohistochemically) in the normal range, while 1 patient had highly increased cytokine levels. In this patient, cytokine levels decreased during treatment. In 4 patients, showing high dermal ICAM-1 expression before treatment, a consistent reduction of ICAM-1 on endothelial cells was observed. The inflammatory infiltrate (T-lymphocytes (T11), monocytes/macrophages (WT14), polymorphonuclear leukocytes (PMN, anti-elastase)) was reduced to some extent after 3 weeks. The number of Langerhans cells (OKT6) did not change. These results indicate that the psoriatic lesions, although clinically comparable, show interindividual differences in cytokine expression. Corticosteroid treatment for 1-3 weeks improves clinical scores and hyperproliferation. Cytokine levels are reduced during steroid treatment in the patient who showed high levels before treatment. To suppress the infiltrate entirely, longer steroid treatment is probably necessary. This may explain the relapse seen after short term corticosteroid therapy.

Administration, Topical↗
PubMed1990

Nitroglycerin and sucrose permeability as quality markers for reconstructed human epidermis.

In order to evaluate the epidermal permeability barrier of in vitro reconstructed epidermis, the penetration of nitroglycerin (NG) and sucrose were measured across human keratinocytes cultured at the air-liquid interface, using de-epidermized dermis (DED) as a substrate. In the presence of reconstructed epidermis on top of DED the penetration rate of sucrose is about 100 times and that of NG 2 times lower, as compared to DED only, indicating that the stratum corneum of the cultured epidermis exhibits considerable barrier capacity. The permeability of reconstructed epidermis was for both solutes higher (3- to 10-fold) than that of freshly excised human skin. Based on the impaired barrier function and distribution of various differentiation markers it can be concluded that the reconstructed human epidermis used in the present study shows a high extent of similarity with hyperproliferating epidermis.

Air↗
PubMed1989

Concepts in immunodermatology.

This review describes the various processes which take place in the immunological network of the skin under physiologic or pathological circumstances. A full understanding of the mechanisms in action is important as it could lead to the development of an entirely new class of therapeutics.

Antigen-Presenting Cells↗
PubMed1988

The influence of pre-incubation on the rate of iron uptake and of transferrin synthesis by intact isolated rat seminiferous tubules.

It has been reported recently that major kinetic differences exist in the rate of iron uptake and of transferrin synthesis between intact seminiferous tubules and cultured Sertoli cells. To investigate possible causes of these differences, intact isolated rat seminiferous tubules were isolated and pre-incubated overnight. Then the rates of iron uptake and of transferrin synthesis were compared with those of freshly isolated tubules. We found that overnight pre-incubation increased the rate of both processes. Iron depletion was not the cause of these changes, since pre-incubation under iron excess gave comparable results. Possible explanations of these phenomena are discussed.

Animals↗
PubMed1988

Kinetics of transferrin endocytosis and iron uptake by intact isolated rat seminiferous tubules and Sertoli cells in culture.

The receptor-mediated endocytotic cycle of rat and human transferrin has been studied in intact, isolated rat seminiferous tubules and Sertoli cells in culture. Double-labeled [( 59Fe125I]) transferrin has been used to study the fate of transferrin and iron. Diferric transferrin binds to the tubules and the cultured Sertoli cells and is internalized. The iron remains inside, while the transferrin recycles and is released into the medium. Although, as reported before (Wauben-Penris et al., 1986), "extra" binding sites for human transferrin exist as compared to rat transferrin, this does not result in extra uptake of transferrin or iron. Both rat and human transferrin transport iron into the cells and recycle back to the surface, and do so with identical kinetics. A striking difference has been found between the mean efficient recycling times of the transferrin receptors in intact tubules (90 min) and in Sertoli cells in culture (21 min). Possible explanations of this difference are discussed. Light-microscopic autoradiography of [125 I]-labeled transferrin has revealed that the transferrin protein is excluded from the adluminal compartment, even after 21 h of incubation. This indicates that externally added transferrin itself does not deliver iron to the postmeiotic germ cells in intact, isolated rat seminiferous tubules.

Animals↗
PubMed1988

The release of iron by Sertoli cells in culture.

In seminiferous tubules, iron transport from the blood to the abluminal germinal cells must occur through the Sertoli cell cytoplasm. We investigated the release of previously accumulated iron by cultured Sertoli cells. We found that Sertoli cells contain easily releasable and less easily releasable iron pools. Iron is released in a low molecular weight form (molecular weight less than 30,000). A high concentration of this low molecular weight iron in the medium reduces further iron release by Sertoli cells, whereas the addition of more medium or fresh medium increases further iron release. Apotransferrin stimulates the release of iron in a dose-dependent manner by chelating the low molecular weight iron. Rat and human apotransferrin are completely competitive in this respect. Diethylenetriamine penta acetic acid (DTPA), an extracellular iron chelator, and apotransferrin compete for iron binding and stimulation of iron release, indicating that no binding or uptake of the chelator by the cells is required. Desferrioxamine (DFO), an intracellular iron chelator, on the other hand, increases iron release more drastically, and apotransferrin cannot compete with it for iron. The addition of extracellular iron also increases the amount of 59Fe in the medium, probably by reducing the re-uptake of 59Fe. This is also demonstrated with primaquine, which blocks endocytosis and increases the amount of 59Fe in the medium. The presence of germinal cells also stimulates the release of iron by Sertoli cells. When cocultured, the germinal cells internalize iron as it is release by Sertoli cells.

Animals↗
PubMed1986

Cell-cell interaction between rat Sertoli cells and mouse germ cells in vitro.

An antiserum against rat germ cell membranes was prepared, and after absorption with protein extracts of rat liver and kidney and mouse testis, this antiserum reacted only with rat germ cell membranes and juxtanuclear vesicles in rat Sertoli cells. Germ cell-free rat Sertoli cell monolayers were cultured in vitro. Freshly isolated mouse germ cells adhered to these monolayers within 1 h. After a minimum of 3 days of such a co-culture, immunofluorescence and immunoblotting revealed that the mouse germ cells had obtained rat-antigenic determinants in their membranes. Our results indicate that this appearance of rat-specific antigens on mouse germ cells is specific and inducible.

Animals↗
PubMed1986

Transferrin receptors of isolated rat seminiferous tubules bind both rat and human transferrin.

The binding and uptake of rat and human transferrin by isolated rat seminiferous tubules was studied. During the isolation and incubation of the tubules, the blood-testis barrier remained intact. Iron-saturated and iron-free (apo-) transferrin use the same binding sites on the surface of the tubules, but the dissociation constant is about two times higher for apotransferrin than for iron-saturated transferrin. The affinity of the receptors is equal for rat and human transferrin, but human transferrin binds to more surface binding sites (2.6 X 10(10) per 10 cm tubule length) than rat transferrin (1.1 X 10(10) per 10 cm tubule length) at 0 degrees C. At 33 degrees C equal numbers of human and rat transferrin molecules are taken up (about 8 X 10(10)) per 10 cm tubule length. The quantitative difference between 0 degrees C and 33 degrees C is caused by the fact that at 33 degrees C receptor-mediated endocytosis and recycling occur. As a consequence, both surface and intracellular transferrin receptors are detected at 33 degrees C. The dissociation constants are not temperature-dependent.

Animals↗
PubMed1985

Spermatogenic delay and increased chiasma frequency in T70H/+ male mice with hydroxyurea-Trenimon limited spermatocyte populations.

T(1;13)70H/+ male mice were treated with hydroxyurea (HU) and Trenimon (T). This karyotype offers excellent possibilities for estimating number and position of chiasmata and segregation in meiotic anaphase I. By their cell-killing action during spermatogenesis, HU and T produce large gaps in the spermatogenic line. The surviving population between the gaps was analysed at diakinesis--metaphase I and metaphase II. We found by autoradiography a considerable retardation of the development from resting primary spermatocytes (RPS) to metaphase I and II as compared to untreated T70H/+ males. Furthermore we found increased chiasma frequencies in diakinesis--metaphase I (MI) and reduced nondisjunction frequencies at anaphse I as a result of the treatments applied. The latter effect could not be explained by the increased chiasma frequency.

Animals↗
PubMed1983

Meiotic behavior of alloxan-treated diabetic and nondiabetic T(;13)70H/+ mice.

The influence of diabetes on first meiotic segregation behavior in female and male T(1;13)70H/+ mice was studied. By treatment with alloxan 60 mg/kg bodyweight both diabetic and non-diabetic control mice were obtained. All female mice were treated with gonadotropins to obtain reasonable numbers of secondary oocytes per female. As a result of this treatment the number of oocytes ovulated and the percentage that could be analyzed were not different in diabetics and controls, indicating that no severe selection occurred as a result of the diabetic state. Male mice were not treated with gonadotropins, and here the low quality of the air-dried preparations and the scarcity of secondary spermatocytes in diabetics suggest that degeneration occurs. In primary spermatocytes we found higher chiasma frequencies in the translocation multivalent in diabetic males than in controls, probably as a result of reduced chiasma terminalization. The analysis of metaphase-II cells in the females revealed less 3:1 segregation and more adjacent-II segregation in the diabetics. In the males no 3:1 segregation was found in either group, but here adjacent-II segregation was lower in diabetics than in controls. No significant differences were found in nondisjunction frequencies of non-translocation-involved bivalents. We conclude that diabetes influences the meiotic segregation behavior of chromosomes and that chromosomes showing higher incidences of unbalanced segregation behavior (i.e., multivalent involved chromosomes) are more susceptible to this influence than other chromosomes. In the diabetic males this influence is undone by the severe selection, affecting primarily the cells, that would give rise to unbalanced metaphase II cells, resulting in even lower frequencies of adjacent-II segregation than in controls.

Animals↗
PubMed1983

Chiasma frequency and nondisjunction in heteromorphic bivalents: meiotic behavior in T(1;13)70H/T(1;13)1Wa mice as compared to T(1;13)70H/T(1;13)70H mice.

Two different reciprocal translocations between chromosomes 1 and 13 in the mouse, T(1;13)70H and T(1;13)1Wa, were intercrossed, resulting in T(1;13)70H/T(1;13)1Wa animals, possessing two heteromorphic marker bivalents. The meiotic behavior of these animals was compared to that of T(1;13)70H/T(1;13)70H animals. In females the chiasma frequency in the translocation bivalents was decreased by the presence of the loops following meiotic pairing, but in males chiasma frequencies were not changes. The nondisjunction level of both translocation bivalents was increased in females and males. The nondisjunction level of bivalents not involved in the translocations was increased in the females, but not in the males. Possible causes and relevance of these phenomena are discussed.

Animals↗
PubMedDate not supplied

Meiotic nondisjunction in male Snell dwarf mice.

Male hypopituitary Snell dwarf mice showed significantly more autosomal univalents in diakinesis-metaphase I (7.75 percent) and more anaphase I nondisjunction (2.68 percent) than normal mice (autosomal univalents: 4.9 percent; nondisjunction: 1.00 percent). The values of male dwarf mice, artificially made hyperthyroid, were between values of untreated dwarfs and normals (autosomal univalents: 5.25 percent; nondisjunction: 2.25 percent), but could not be shown to differ significantly from either value.

Animals↗
PubMedDate not supplied

Meiotic nondisjunction and translocation segregation in dwarf (dw/dw) and control T(1;13)70H heterozygous mice.

The meiotic behavior of translocation heterozygous T70 (1;13)H/+ male mice with a Snell dwarf (dw/dw) genotype was compared with that of nondwarf T70H/+ controls. A four-fold increase in the nondisjunction frequency of the normal bivalents occurred as a consequence of the dwarf genotype. This increase is identical to that seen in karyologically normal dwarf males. No effect of the dwarf condition on the segregation of the translocation multivalent could be noted. Thus, translocation heterozygosity does not enhance the meiotic instability caused by the hypopituitary dwarf condition. From a small sample of oocytes from T70H/+ and chromosomally normal dwarf females it is concluded that nondisjunction in females is not increased by the dwarf condition. In general we conclude that animals with higher spontaneous nondisjunction levels are not necessarily more sensitive to factors increasing nondisjunction.

Animals↗